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c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas.
[liposarcoma]
Genomic
amplification
of
the
c-
Jun
proto-oncogene
has
been
identified
in
∼
30
%
of
dedifferentiated
liposarcomas
(
DDLPS
)
,
but
the
functional
contribution
of
c-
Jun
to
the
progression
of
DDLPS
remains
poorly
understood
.
In
previous
work
we
showed
that
knock-down
of
c-
Jun
by
RNA
interference
impaired
the
in
vitro
proliferation
and
in
vivo
growth
of
a
DDLPS
cell
line
(
LP
6
)
with
genomic
amplification
of
the
c-
Jun
locus
.
Here
,
we
used
gene
expression
analysis
and
functional
studies
in
a
broad
panel
of
cell
lines
to
further
define
the
role
of
c-
Jun
in
DDLPS
and
other
soft
tissue
sarcomas
.
We
show
that
c-
Jun
knock-down
impairs
transition
through
the
G
1
phase
of
the
cell
cycle
in
multiple
DDLPS
cell
lines
.
We
also
found
that
high
levels
of
c-
Jun
expression
are
both
necessary
and
sufficient
to
promote
DDLPS
cell
migration
and
invasion
in
vitro
.
Our
data
suggest
that
high
levels
of
c-
Jun
enhance
motility
in
part
by
driving
the
expression
of
ENPP
2
/
Autotaxin
.
c-
Jun
over-expression
has
minimal
effects
on
in
vitro
proliferation
but
substantially
enhances
the
in
vivo
growth
of
weakly
tumourigenic
DDLPS
cell
lines
.
Finally
,
we
provide
evidence
that
c-
Jun
genomic
amplification
and
over-expression
may
have
similar
functional
consequences
in
other
types
of
soft
tissue
sarcoma
.
Our
data
suggest
a
model
in
which
relatively
low
levels
of
c-
Jun
are
sufficient
for
in
vitro
proliferation
,
but
high
levels
of
c-
Jun
enhance
invasiveness
and
capacity
for
in
vivo
tumour
growth
.
These
observations
provide
an
explanation
for
the
selective
advantage
provided
by
c-
Jun
genomic
amplification
in
vivo
and
suggest
that
sarcomas
with
elevated
c-
Jun
levels
are
likely
to
have
a
particularly
high
malignant
potential
.
Data
from
exon
array
and
RNA-Seq
experiments
have
been
deposited
in
the
GEO
database
(
Accession
No
.
GSE
57531
)
.
Diseases
Validation
Diseases presenting
"high levels"
symptom
22q11.2 deletion syndrome
adrenal incidentaloma
allergic bronchopulmonary aspergillosis
alpha-thalassemia
aromatase deficiency
cadasil
canavan disease
classical phenylketonuria
congenital adrenal hyperplasia
congenital toxoplasmosis
cutaneous mastocytosis
cystinuria
dentin dysplasia
dentinogenesis imperfecta
dracunculiasis
dystrophic epidermolysis bullosa
erythropoietic protoporphyria
gm1 gangliosidosis
hereditary cerebral hemorrhage with amyloidosis
holt-oram syndrome
homocystinuria without methylmalonic aciduria
kabuki syndrome
kallmann syndrome
liposarcoma
papillon-lefèvre syndrome
phenylketonuria
primary effusion lymphoma
primary hyperoxaluria type 1
scrub typhus
severe combined immunodeficiency
systemic capillary leak syndrome
triple a syndrome
von hippel-lindau disease
werner syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
zellweger syndrome
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